2′–5′ oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability

Tae Kyeong Kim, Sejin Jeon, Seonjun Park, Seong-Keun Sonn, Seungwoon Seo, Joowon Suh, Jing Jin, Hyae Yon Kweon, Sinai Kim, Shin Hye Moon, Okhee Kweon, Bon-Hyeock Koo, Nayoung Kim, Hae-Ock Lee, Young-Myeong Kim, Young-Joon Kim, Sung Ho Park and Goo Taeg Oh ()
Additional contact information
Tae Kyeong Kim: Ewha Womans University
Sejin Jeon: Ewha Womans University
Seonjun Park: Ulsan National Institute of Science & Technology (UNIST)
Seong-Keun Sonn: Ewha Womans University
Seungwoon Seo: Ewha Womans University
Joowon Suh: Ewha Womans University
Jing Jin: Ewha Womans University
Hyae Yon Kweon: Ewha Womans University
Sinai Kim: Ewha Womans University
Shin Hye Moon: Ewha Womans University
Okhee Kweon: Ewha Womans University
Bon-Hyeock Koo: Kangwon National University
Nayoung Kim: The Catholic University of Korea
Hae-Ock Lee: The Catholic University of Korea
Young-Myeong Kim: Kangwon National University
Young-Joon Kim: Yonsei University
Sung Ho Park: Ulsan National Institute of Science & Technology (UNIST)
Goo Taeg Oh: Ewha Womans University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Endothelial nitric oxide synthase (eNOS) decreases following inflammatory stimulation. As a master regulator of endothelial homeostasis, maintaining optimal eNOS levels is important during cardiovascular events. However, little is known regarding the mechanism of eNOS protection. In this study, we demonstrate a regulatory role for endothelial expression of 2′–5′ oligoadenylate synthetase-like 1 (OASL1) in maintaining eNOS mRNA stability during athero-prone conditions and consider its clinical implications. A lack of endothelial Oasl1 accelerated plaque progression, which was preceded by endothelial dysfunction, elevated vascular inflammation, and decreased NO bioavailability following impaired eNOS expression. Mechanistically, knockdown of PI3K/Akt signaling-dependent OASL expression increased Erk1/2 and NF-κB activation and decreased NOS3 (gene name for eNOS) mRNA expression through upregulation of the negative regulatory, miR-584, whereas a miR-584 inhibitor rescued the effects of OASL knockdown. These results suggest that OASL1/OASL regulates endothelial biology by protecting NOS3 mRNA and targeting miR-584 represents a rational therapeutic strategy for eNOS maintenance in vascular disease.

Date: 2022
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DOI: 10.1038/s41467-022-34433-z

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